7RCW

Crystal structure of C. difficile penicillin-binding protein 2 in complex with ampicillin

7RCW の概要

• エントリーDOI: 10.2210/pdb7rcw/pdb
• 分子名称: Penicillin-binding protein, DI(HYDROXYETHYL)ETHER, ACETATE ION, ... (7 entities in total)
• 機能のキーワード: peptidoglycan, pbp, pbp2, cell wall, transpeptidase, b-lactam, gram-positive, spore, sporulation, peptide binding protein
• 由来する生物種: Clostridioides difficile (strain R20291) (Peptoclostridium difficile)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 104670.55

構造登録者

Sacco, M.,Chen, Y. (登録日: 2021-07-08, 公開日: 2022-03-23, 最終更新日: 2023-10-18)

主引用文献

Sacco, M.D.,Wang, S.,Adapa, S.R.,Zhang, X.,Lewandowski, E.M.,Gongora, M.V.,Keramisanou, D.,Atlas, Z.D.,Townsend, J.A.,Gatdula, J.R.,Morgan, R.T.,Hammond, L.R.,Marty, M.T.,Wang, J.,Eswara, P.J.,Gelis, I.,Jiang, R.H.Y.,Sun, X.,Chen, Y.
A unique class of Zn 2+ -binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile.
Nat Commun, 13:4370-4370, 2022

PubMed Abstract: Treatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor for Clostridioides difficile infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However, C. difficile has four different PBPs (PBP1-3 and SpoVD) with various roles in growth and spore formation, and their specific links to β-lactam resistance in this pathogen are underexplored. Here, we show that PBP2 (known to be essential for vegetative growth) is the primary bactericidal target for β-lactams in C. difficile. PBP2 is insensitive to cephalosporin inhibition, and this appears to be the main basis for cephalosporin resistance in this organism. We determine crystal structures of C. difficile PBP2, alone and in complex with β-lactams, revealing unique features including ligand-induced conformational changes and an active site Zn-binding motif that influences β-lactam binding and protein stability. The Zn-binding motif is also present in C. difficile PBP3 and SpoVD (which are known to be essential for sporulation), as well as in other bacterial taxa including species living in extreme environments and the human gut. We speculate that this thiol-containing motif and its cognate Zn might function as a redox sensor to regulate cell wall synthesis for survival in adverse or anaerobic environments.

PubMed: 35902581
DOI: 10.1038/s41467-022-32086-6

実験手法

X-RAY DIFFRACTION (3 Å)